{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:10Z","timestamp":1785437950633,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,31]]},"group-title":"Immunology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R35GM137801"],"award-info":[{"award-number":["R35GM137801"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["F31AI179201"],"award-info":[{"award-number":["F31AI179201"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Acute myeloid leukemia (AML) is a heterogeneous disease that arises from dysregulated myeloid proliferation. We performed a high-throughput CRISPR interference (CRISPRi) screen in the THP-1 monocytic cancer cell line to identify long noncoding RNAs (lncRNAs) that play a role in contributing to cell proliferation. Our screen identified\n                  <jats:italic>INSTAR<\/jats:italic>\n                  (Intergenic Nuclear Suppressor lncRNA Targeting Adjacent Regulator\n                  <jats:italic>SFMBT2<\/jats:italic>\n                  ) as a top candidate. RNA-seq on\n                  <jats:italic>INSTAR<\/jats:italic>\n                  deficient THP-1 cells revealed transcriptional changes in genes involved in cell proliferation as well as other cellular processes. Loss of\n                  <jats:italic>INSTAR<\/jats:italic>\n                  selectively reduced expression of its neighboring gene,\n                  <jats:italic>SFMBT2<\/jats:italic>\n                  . Functional assays confirmed that both genes suppress cell growth, revealing a cis-regulatory mechanism in which\n                  <jats:italic>INSTAR<\/jats:italic>\n                  regulates\n                  <jats:italic>SFMBT2<\/jats:italic>\n                  expression to control monocyte proliferation. Here, we leverage high-throughput screening to rapidly pinpoint functional lncRNAs providing novel insights into a key regulatory locus consisting of\n                  <jats:italic>INSTAR<\/jats:italic>\n                  and\n                  <jats:italic>SFMBT2<\/jats:italic>\n                  which could be critical for better understanding dysregulation contributing to acute myeloid leukemia.\n                <\/jats:p>","DOI":"10.1101\/2025.10.30.685589","type":"posted-content","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T20:35:19Z","timestamp":1761942919000},"source":"Crossref","is-referenced-by-count":0,"title":["CRISPRi Screen Identifies a Novel Growth Suppressor lncRNA,\n                  <i>INSTAR<\/i>\n                  , in Human Monocytes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7027-8458","authenticated-orcid":false,"given":"Christy","family":"Montano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Malekos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Covarrubias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Katzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Sudek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-5404","authenticated-orcid":false,"given":"Susan","family":"Carpenter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025110404050450000_2025.10.30.685589v1.1","unstructured":"Childhood and Adolescent Blood Cancer Facts and Statistics | Blood Cancer United. [accessed 2025 Oct 24]. https:\/\/bloodcancerunited.org\/childhood-and-adolescent-blood-cancer-facts-and-statistics"},{"key":"2025110404050450000_2025.10.30.685589v1.2","unstructured":"What Is Acute Myeloid Leukemia (AML)? | American Cancer Society. [accessed 2025 Oct 24]. https:\/\/www.cancer.org\/cancer\/types\/acute-myeloid-leukemia\/about\/what-is-aml.html"},{"key":"2025110404050450000_2025.10.30.685589v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-025-01351-3"},{"key":"2025110404050450000_2025.10.30.685589v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1078"},{"key":"2025110404050450000_2025.10.30.685589v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah7111"},{"key":"2025110404050450000_2025.10.30.685589v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2322524121"},{"key":"2025110404050450000_2025.10.30.685589v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.027"},{"key":"2025110404050450000_2025.10.30.685589v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016648118"},{"key":"2025110404050450000_2025.10.30.685589v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251456"},{"key":"2025110404050450000_2025.10.30.685589v1.10","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2024.2417155"},{"key":"2025110404050450000_2025.10.30.685589v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.068"},{"key":"2025110404050450000_2025.10.30.685589v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.10.011"},{"key":"2025110404050450000_2025.10.30.685589v1.13","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-025-01810-z"},{"key":"2025110404050450000_2025.10.30.685589v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.184"},{"key":"2025110404050450000_2025.10.30.685589v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81715-5"},{"key":"2025110404050450000_2025.10.30.685589v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.10.021"},{"key":"2025110404050450000_2025.10.30.685589v1.17","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-016-0059-9"},{"key":"2025110404050450000_2025.10.30.685589v1.18","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11111638"},{"key":"2025110404050450000_2025.10.30.685589v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.110204"},{"key":"2025110404050450000_2025.10.30.685589v1.20","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10198"},{"key":"2025110404050450000_2025.10.30.685589v1.21","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092718"},{"key":"2025110404050450000_2025.10.30.685589v1.22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2400718"},{"key":"2025110404050450000_2025.10.30.685589v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.215958"},{"key":"2025110404050450000_2025.10.30.685589v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.029"},{"key":"2025110404050450000_2025.10.30.685589v1.25","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.02.23"},{"key":"2025110404050450000_2025.10.30.685589v1.26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044152"},{"key":"2025110404050450000_2025.10.30.685589v1.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2213056120"},{"key":"2025110404050450000_2025.10.30.685589v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100784"},{"key":"2025110404050450000_2025.10.30.685589v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.08.006"},{"key":"2025110404050450000_2025.10.30.685589v1.30","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16233974"},{"key":"2025110404050450000_2025.10.30.685589v1.31","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17172874"},{"key":"2025110404050450000_2025.10.30.685589v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00506-6"},{"key":"2025110404050450000_2025.10.30.685589v1.33","doi-asserted-by":"publisher","DOI":"10.1186\/s13062-024-00480-3"},{"key":"2025110404050450000_2025.10.30.685589v1.34","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02156-8"},{"key":"2025110404050450000_2025.10.30.685589v1.35","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3978"},{"key":"2025110404050450000_2025.10.30.685589v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108541"},{"key":"2025110404050450000_2025.10.30.685589v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2669"},{"key":"2025110404050450000_2025.10.30.685589v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-021-00606-6"},{"key":"2025110404050450000_2025.10.30.685589v1.39","doi-asserted-by":"publisher","DOI":"10.1242\/dev.096511"},{"key":"2025110404050450000_2025.10.30.685589v1.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac972"},{"key":"2025110404050450000_2025.10.30.685589v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.11.036"},{"key":"2025110404050450000_2025.10.30.685589v1.42","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad993"},{"key":"2025110404050450000_2025.10.30.685589v1.43","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-204"},{"key":"2025110404050450000_2025.10.30.685589v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/nature20149"},{"key":"2025110404050450000_2025.10.30.685589v1.45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.799155"},{"key":"2025110404050450000_2025.10.30.685589v1.46","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-4035-6_1"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.30.685589","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:56:12Z","timestamp":1768470972000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.30.685589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":46,"URL":"https:\/\/doi.org\/10.1101\/2025.10.30.685589","relation":{},"subject":[],"published":{"date-parts":[[2025,10,31]]},"subtype":"preprint"}}